Evaluation of Adherent Invasive E. Coli Eradication in Adult Crohn Disease

Phase 2

Terminated

• Conditions: Crohn Disease; Adherent-invasive E. Coli
• Interventions: Drug: Ciprofloxacin; Drug: Ciprofloxacin Placebo; Drug: Rifaximin; Drug: Rifaximin Placebo

• Registration Number: NCT02620007
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The primary objective of this trial is to assess whether a 12-week treatment with Ciprofloxacin and Rifaximin is superior to placebo to obtain endoscopic remission in adherent-invasive E. coli (AIEC)-colonized patients with ileal Crohn disease (CD), with or without involvement of the caecum or the right colon.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-30
• Study Start: 2015-12
• Study First Submitted QC: 2015-12-01
• Study First Posted: 2015-12-02
• Status Verified: 2019-02
• Primary Completion: 2021-08
• Study Completion: 2022-06
• Last Update Submitted: 2023-08-21
• Last Update Posted: 2023-08-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• CD of the ileum, with or without involvement of the caecum or the right colon
• Colonoscopy showing active lesions defined by a CDEISm score >6
• Informed consent to participate in this study
• Prescription of steroid treatments : Budesonide, Prednisone (or Prednisolone) independently from entry in study
• Patients who respond to budesonide (initial dose 9 mg/d) or prednisone or prednisolone (initial dose 40 mg/d), defined as a 70 points decrease in CDAI between the pre-inclusion and the inclusion visit,
• Patients colonized with AIEC on initial ileal biopsies.

Exclusion Criteria

• Ileal stenosis that cannot be crossed by the endoscope,
• Infliximab treatment received less than 8 weeks before inclusion in this study,
• Adalimumab treatment received less than 4 weeks before inclusion in this study,
• Vedolizumab treatment received less than 8 weeks before inclusion in the study,
• Hypersensitivity to Ciprofloxacin, to other quinolones, or to any of the excipients (cellulose microcrystalline, crospovidone, maize starch, magnesium stearate, silica colloidal anhydrous,, hypromellose titanium dioxide E171, macrogol 4000,),
• Tizanidine, Probenecid, Theophylline, Xanthine derivatives, Phenytoin, oral anticoagulants, and Ropinirole treatment,
• Hypersensitivity to Rifaximin, or to any excipients (sodium starch glycolate type A, glycerol distearate, colloidal anhydrous silica, talc, microcrystalline cellulose, hypromellose, titanium dioxide, disodium edentate, propylene glycol, red iron oxide E172),
• Previous extensive ileal surgery (≥ 1 meter as measured on the pathology and/or surgical report),
• Short bowel syndrome,
• Need for an intestinal resection for fistula, abscess or intestinal obstruction,
• Renal failure (creatinine clearance<30 mL/min/1.73m2),
• Liver failure (V factor<50%),
• Past history of epilepsy,
• No health insurance,
• Pregnant or lactating women,
• Refusal to have a double effective contraception,
• Patients already included in a biomedical research other than an observational study (e.g: registry, cohort).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental arm	Ciprofloxacin	oral Ciprofloxacin 500 mg bid and oral Rifaximin 800 mg bid for 12 weeks
Experimental arm	Rifaximin	oral Ciprofloxacin 500 mg bid and oral Rifaximin 800 mg bid for 12 weeks
Control arm	Ciprofloxacin Placebo	a placebo of Ciprofloxacin bid and a placebo of Rifaximin bid for 12 weeks
Control arm	Rifaximin Placebo	a placebo of Ciprofloxacin bid and a placebo of Rifaximin bid for 12 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of patients with Endoscopic Endoscopic Index of Severity (CDEISm)< 6 and a decrease in CDEISm ≥ 3	week 12	(assessed within each site quotation), defined by the modified Crohn's Disease Endoscopic Index of Severity (CDEISm)\< 6 and a decrease in CDEISm ≥ 3, as compared to baseline values.

Secondary Outcome Measures

Name	Time	Method
Microbiota composition	weeks 12 and 48
Complete endoscopic remission	week 12	assessed by centralized, anonymous and blinded reading of ileocolonoscopies, and defined by a CDEISm \<3
Biological remission	weeks 4, 8, 12, 24, 36 and 48	defined by haemoglobin level ≥13g/dL and C-Reactive Protein (CRP) serum level ≤5 mg/L and fecal calprotectin \<300 mg/L
Mean variation of CDEISm	week 12	assessed by centralized, anonymous and blinded reading of ileocolonoscopies
Clinical remission	12 and 48 weeks	defined by Crohn's disease activity index (CDAI)\<150 without steroids, anti-Tumor Necrosis Factor (TNF), and surgery
lpf positive AIEC bacteria in the stools	weeks 12 and 48	Detection (by PCR)
Side effects	week 12	adverse events
No ulceration	week 12

Trial Locations

Locations (2)

Gastroenterology department; 🇫🇷 Le Kremlin Bicetre, France

Kremlin-Bicetre hospital; 🇫🇷 Le Kremlin-Bicêtre, France